Differential Treatment Efficacy Research Articles

Cost-effectiveness of methods in personalized medicine. Results of a decision-analytic model in patients with acute myeloid leukemia with normal karyotype

BackgroundDuring the last years, molecular genetic data are increasingly used as prognostic and predictive factors in acute myeloid leukemia (AML). The molecular genetic profile permits a rapid risk categorization and beyond that a prediction of differential treatment efficacy of post-remission chemotherapy versus an allogeneic hematopoietic cell transplantation (HCT) in specific subgroups. MethodsThe aim of this study was to evaluate cost-effectiveness of two different strategies of risk categorization (conventional cytogenetic diagnostics (CCD) versus molecular genetic diagnostics (MGD)) in patients with AML, using a decision-analytic state-transition model. The model is run as (Monte Carlo) microsimulation in which individuals pass through in cycles with a cycle length of one month and a time horizon of ten years. FindingsResults show that on average, individuals within the MGD group generated about US$ 32,000 higher costs but survived about seven months longer than individuals within the CCD group. This leads to an Incremental Cost-Effectiveness Ratio (ICER) of about US$ 4928 per survived month. InterpretationWith a GDP (Gross Domestic Product) of US$ 26,467 (€ 33,630) per capita in Germany in 2012, the base-case ICER of US$ 4928 per survived month projected to US$ 59,136 per survived year is in between the simple GDP and the three times GDP per capita.

Psychopharmacological treatment of psychotic mania and psychotic bipolar depression compared to non-psychotic mania and non-psychotic bipolar depression.

An evidence base for the treatment of mania and bipolar depression with psychotic symptoms is lacking. Nevertheless, clinicians may have a preference for treating episodes of bipolar disorder with or without psychotic symptoms in different ways, which is likely to reflect notions of differential efficacy of treatments between these subtypes. This study aimed to investigate whether the psychopharmacological treatment of psychotic and non-psychotic episodes of mania and bipolar depression, respectively, differs in clinical practice. We conducted a register-based study assessing the psychopharmacological treatment of all individuals receiving their first diagnosis of mania or bipolar depression between 2010 and 2012. The psychopharmacological treatment within 3months following the time of diagnosis was considered. Potential differences in psychopharmacological treatment between the psychotic and non-psychotic subtypes of mania and bipolar depression, respectively, were investigated by means of Pearson's χ2 test and logistic regression adjusted for sex and age at diagnosis of bipolar disorder. A total of 827 patients were included in the analyses. The adjusted odds ratio (aOR) for treatment with an antipsychotic was 1.71 (95% confidence interval [CI]: 1.18-2.48, P<.01) for psychotic mania and 3.89 (95% CI: 1.95-7.76, P<.001) for psychotic bipolar depression. The aOR for treatment with the combination of an antipsychotic and an anticonvulsant was 1.60 (95% CI: 1.06-2.43, P<.05) for psychotic mania. The aOR for treatment with the combination of an antipsychotic and an antidepressant was 2.50 (95% CI: 1.43-4.37, P<.01) for bipolar psychotic depression. It would be of interest to conduct studies evaluating whether antipsychotics represent the superior pharmacological treatment for psychotic mania and psychotic bipolar depression.

Do Psychiatric Disorders or Measures of Distress Moderate Response to Postpartum Relapse Prevention Interventions?

Most women who quit smoking during pregnancy will relapse postpartum. Interventions for sustained postpartum abstinence can benefit from understanding prenatal characteristics associated with treatment response. Given that individuals with psychiatric disorders or elevated depressive symptoms have difficulty quitting smoking and that increases in depressive symptoms prenatally are common, we examined the relevance of psychiatric diagnoses, prenatal depressive symptoms, and stress to postpartum relapse prevention intervention response. Pregnant women (N = 300) who quit smoking during pregnancy received intervention (with specialized focus on mood, weight, and stress [STARTS] or a comparison [SUPPORT]) to prevent postpartum relapse. As previously published, nearly one-third and one-quarter of women achieved biochemically-confirmed sustained abstinence at 24- and 52-weeks postpartum, with no difference in abstinence rates between the interventions. Women completed psychiatric interviews and questionnaires during pregnancy. Smoking was assessed in pregnancy, and 24- and 52-weeks postpartum. Psychiatric disorders did not predict sustained abstinence or treatment response. However, treatment response was moderated by end-of-pregnancy depressive symptoms (χ2 = 9.98, p = .002) and stress (χ2 = 6.90, p = .01) at 24- and 52-weeks postpartum and remained significant after including covariates. Women with low distress achieved higher abstinence rates in SUPPORT than in STARTS (37% vs. 19% for depressive symptoms; 36% vs. 19% for stress), with no difference for women with high symptoms. Prenatal depressive symptoms and stress predicted differential treatment efficacy in women with low symptoms, not in women with high symptoms. Diagnostic history did not predict treatment differences. Future research to address prenatal distress may help tailor postpartum relapse prevention interventions. We examined prenatal history of psychiatric disorders and psychiatric distress as moderators of response to postpartum smoking relapse prevention intervention that either included or did not include added content on mood, stress, and weight concerns. For women with lower psychiatric distress, the added focus is not necessary, as these women achieved greater sustained abstinence in the less-intensive treatment. Understanding which women need which level of care to sustain abstinence can help allocate resources for all postpartum former smokers. These findings underscore the importance of perinatal symptom monitoring and promoting behavioral health more broadly in pregnant and postpartum women.

Magnetic resonance perfusion image features uncover an angiogenic subgroup of glioblastoma patients with poor survival and better response to antiangiogenic treatment.

In previous clinical trials, antiangiogenic therapies such as bevacizumab did not show efficacy in patients with newly diagnosed glioblastoma (GBM). This may be a result of the heterogeneity of GBM, which has a variety of imaging-based phenotypes and gene expression patterns. In this study, we sought to identify a phenotypic subtype of GBM patients who have distinct tumor-image features and molecular activities and who may benefit from antiangiogenic therapies. Quantitative image features characterizing subregions of tumors and the whole tumor were extracted from preoperative and pretherapy perfusion magnetic resonance (MR) images of 117 GBM patients in 2 independent cohorts. Unsupervised consensus clustering was performed to identify robust clusters of GBM in each cohort. Cox survival and gene set enrichment analyses were conducted to characterize the clinical significance and molecular pathway activities of the clusters. The differential treatment efficacy of antiangiogenic therapy between the clusters was evaluated. A subgroup of patients with elevated perfusion features was identified and was significantly associated with poor patient survival after accounting for other clinical covariates (P values <.01; hazard ratios > 3) consistently found in both cohorts. Angiogenesis and hypoxia pathways were enriched in this subgroup of patients, suggesting the potential efficacy of antiangiogenic therapy. Patients of the angiogenic subgroups pooled from both cohorts, who had chemotherapy information available, had significantly longer survival when treated with antiangiogenic therapy (log-rank P=.022). Our findings suggest that an angiogenic subtype of GBM patients may benefit from antiangiogenic therapy with improved overall survival.

Regression to the Mean: A Commonly Overlooked and Misunderstood Factor Leading to Unjustified Conclusions in Pediatric Obesity Research.

In this paper we discuss what regression to the mean (RTM) is, the magnitude of RTM in realistic situations, interpretation of RTM, and recommendations for how to address RTM in study design. Public health research faces many challenges in conducting gold standard randomized, controlled trials (RCT). Although there are many threats to validity in uncontrolled trials, RTM is often overlooked or not adequately considered. RTM is a statistical phenomenon that occurs with any pair of variables that have a correlation not equal to |1.0|. With RTM, subjects' average values on an outcome variable (e.g., BMI) change in a systematic direction over time despite there being no treatment effect. Without a proper control group, changes thought to be associated with an intervention may be due entirely to RTM. Investigators may draw erroneous conclusions based on results showing greater declines in a variable among participants with higher baseline of that variable compared to those with lower baseline of that variable, and label this evidence for differential treatment efficacy. Ignoring RTM can lead to unsubstantiated conclusions about the effects of treatments. These conclusions can lead to the waste of time, money, and other resources, which distract from finding appropriate interventions. When a true RCT design is not feasible, reasonable design alternatives involving nonrandomized control groups should be implemented.

Subgroup mixable inference on treatment efficacy in mixture populations, with an application to time-to-event outcomes.

In tailored drug development, the patient population is thought of as a mixture of two or more subgroups that may derive differential treatment efficacy. To find the right patient population for the drug to target, it is necessary to infer treatment efficacy in subgroups and combinations of subgroups. A fundamental consideration in this inference process is that the logical relationships between treatment efficacy in subgroups and their combinations should be respected (for otherwise the assessment of treatment efficacy may become paradoxical). We show that some commonly used efficacy measures are not suitable for a mixture population. We also show that the current practice of over-simply extending the least squares means concept when estimating the efficacy in a mixture population is inappropriate. Proposing a new principle called subgroup mixable estimation, we establish the logical relationships among parameters that represent efficacy and develop a simultaneous inference procedure to confidently infer efficacy in subgroups and their combinations. Using oncology studies with time-to-event outcomes as an example, we show that the hazard ratio is not suitable for measuring treatment efficacy in a mixture population and provide appropriate efficacy measures with a rigorous inference procedure.

A Subgroup Analysis Found no Diminished Response to Buprenorphine Transdermal System Treatment for Chronic Low Back Pain Patients Classified with Depression.

Chronic pain (CP) patients with depression typically exhibit worse post-treatment outcomes than nondepressed CP patients. The cause is often assumed to reflect a differential response to treatment, neglecting other potential explanations, such as the continuation of differences in pretreatment outcomes. This post hoc analysis examines whether worse post-treatment outcomes for depressed patients with chronic low back pain (CLBP) are driven by reduced treatment efficacy. Data were from opioid-naïve adult patients with moderate-to-severe CLBP who participated in a randomized, placebo-controlled, double-blind clinical trial of Butrans(®) (buprenorphine) Transdermal System (BTDS) for pain relief. Depression screening was based on baseline SF-36v2 Mental Health subscale scores. Patient-reported measures of pain severity, pain interference, quality of life, sleep problems, and functional disability were administered at screening and during the study. Differential treatment efficacy for each outcome was examined using analysis of covariance models that included interaction terms between treatment arm and depression status. At baseline, patients classified as depressed showed greater pain interference, lower quality of life, more sleep problems, and greater functional disability than nondepressed patients; the two groups did not differ in pain severity. No statistically significant interactions between treatment arm and depression status were observed. The direction of improvement post-treatment favored the depressed group on nine of seventeen outcomes. Results do not support a differential response to BTDS treatment between depressed and nondepressed CLBP patients across a variety of patient-reported outcomes. These findings raise the question of whether depressed mood actually moderates the effectiveness of treatment in CP patients.

P.1.i.005 Acute neural effects of SSRIs versus NRIs on emotion processing: implications for differential treatment efficacy

P.1.i.005 Acute neural effects of SSRIs versus NRIs on emotion processing: implications for differential treatment efficacy

SP0195 Pediatric central nervous system vasculitis

Childhood CNS vasculitis is an increasingly recognized inflammatory brain disease, which may develop as a primary condition, or secondary to an underlying systemic illness. Primary angiitis of the central nervous...

Relative effectiveness of adjunctive risperidone on manic and depressive symptoms in mixed mania

Mixed states are common and severe manifestations of bipolar disorder, with limited data on the differential efficacy of treatments on depressive and manic symptoms. This study assessed the effectiveness of open-label adjunctive risperidone in achieving sustained effectiveness in patients with mixed mania, with a specific focus on the differential benefits on manic and depressive symptomatology. Forty patients with bipolar disorder I, currently in a mixed manic episode, were treated with adjunctive risperidone. Behavioral measures at baseline and weeks 1, 2, 4, 8, 12, 16, and 20 were assessed using the following scales: the Young Mania Rating Scale, the Montgomery Asberg Depression Rating Scale (MADRS), and the Global Assessment Scale. The primary outcome measure was the proportion of patients who attained a sustained response on either depressive or manic symptomatology, defined as at least 50% reduction from the baseline on the Montgomery Asberg Depression Rating Scale or the Young Mania Rating Scale, maintained over at least 8 weeks without subsequent relapse during the 20-week trial. A significantly higher proportion of patients achieved a sustained response for mania than depression, 16/40 versus 6/40, respectively (McNemar's χ² 8.33, P=0.004). Higher elevated mood at baseline and lower apparent sadness (P<0.016) each predicted a sustained response for mania (P<0.0001). Mixed manic patients who were treated with risperidone adjunctive to mood stabilizer/s for 20 weeks were significantly more likely to achieve a sustained response for manic than for depressive symptomatology.

Abstract 69: Can Patient or Arterial Characteristics Guide the Choice between Carotid Angioplasty and Carotid Endarterectomy? The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)

Background: We have previously reported that carotid artery stenting (CAS) carries a higher stroke risk than carotid endarterectomy (CEA) in patients over the age of 70. The question arises if advanced age is a surrogate for other factors? If so, can those factors be separately identified such that advanced chronological age alone would not be considered a contra-indication for CAS? Here we consider whether the CAS/CEA choice could be guided by other factors known in the clinical center at the time of patient evaluation, independent of age, in order to provide optimal 4-year outcomes. Methods: Demographic factors (age, sex and race), symptomatic status, patient risk factors (hypertension, diabetes, dyslipidemia, smoking), and arterial characteristics (percent stenosis) were available on 2,502 patients. Additional detailed arterial characteristics (ulcerated plaque, distal tortuosity, sequential lesions, circumferential calcification) were available on 1141 CAS and 438 CEA patients. Potential differential treatment efficacy was assessed by the addition of factor-by-treatment interaction terms to a proportional hazard model containing established predictors of outcome (treatment, symptomatic status, sex, age and age-by-treatment interaction). Results: No other factor was found to mitigate advanced age with evidence of additional treatment effect modification of 4-year outcome (p &gt; 0.10). Discussion: Beyond the previously described differential treatment efficacy by age, there were no other patient or arterial characteristic detected to identify patient subgroups that would differentially benefit from the choice of CAS versus CEA. Our inability to identify factors to guide treatment choices could be due to the low number of stroke and death events, incomplete information regarding arterial characteristics in the CEA population, or the potential exclusion of “high risk” groups (such as those with severe arterial tortuosity) from the study.

Quality of Life Analysis of TORCH, a Randomized Trial Testing First-Line Erlotinib Followed by Second-Line Cisplatin/Gemcitabine Chemotherapy in Advanced Non–Small-Cell Lung Cancer

The TORCH (Tarceva or Chemotherapy) trial randomized patients with advanced non-small-cell lung cancer to first-line erlotinib followed by second-line cisplatin/gemcitabine versus. standard inverse sequence. The trial, designed to test noninferiority in overall survival, was stopped at interim analysis because of inferior survival in the experimental arm. Quality of life (QoL), a secondary outcome, is reported here. QoL was assessed at baseline and every 3 weeks during first-line, using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 and QLQ-lung cancer specific module (LC13). Mean changes from baseline within arms were reported. QoL response and time-to-deterioration of QoL using a competing-risk approach were compared between treatment arms. Six hundred and thirty patients (83%) completed baseline questionnaires. Compliance was affected by differential treatment efficacy, but was similar between arms for patients without progression or death. Significant differences in QoL responses were observed favoring chemotherapy for pain, sleeping, dyspnea, diarrhea, and favoring erlotinib for vomiting, constipation, sore mouth, and alopecia. In the small subset of patients with EGFR-mutated tumors, all selected items (global QoL, physical functioning, cough, dyspnea and pain) improved, whereas worsening or no change was observed in wild-type patients. Improvement was particularly evident in the first-line erlotinib arm as for global QoL and physical functioning. QoL was impacted by differential toxicity and efficacy between arms. Functional domains and global QoL did not differ, although some symptoms were better controlled with chemotherapy in unselected non-small-cell lung cancer patients.

Differential Efficacy of Home Monitoring and Cognitive-Behavioral Treatment for Decreasing Children's Maladaptive Nighttime Fears

A number of studies have demonstrated the efficacy of brief cognitive-behavioral interventions for treating childhood nighttime fears. The purpose of the present study is to determine whether behavior changes could be initiated and maintained with home monitoring and reinforcement alone. Sixteen children, ages 6 to 11, with severe, disruptive nighttime fears were assigned to either a group receiving only reinforcement and home monitoring or a group receiving reinforcement and home monitoring plus an additional skills component. Results reveal that both groups show a significant reduction in the intensity and frequency of nighttime fears. However, only the group receiving the full treatment package maintained these gains over time.

Differential efficacy of standard inpatient treatment between Mormon and non-Mormon patients

Despite differences in doctrine and belief structure, much of current research and most therapeutic practice continue to treat the thirty six recognised denominations of Christianity identically. Analysis of 298 inpatients (37.6% Mormon) at a large state psychiatric hospital found differential efficacy based on denomination (Mormon versus Non-Mormon) on seven of the 24 items of the Brief Psychiatric Rating Scale. Differential efficacy of treatment was also found based on gender for four of the 24 items with those differences possibly stemming from gender differences in openness to therapy. Finally, two denominations by gender interactions were noted as well. Taken together, the results of the current study indicate that specific denomination membership may have a more significant impact on the outcome of therapy than current practice implies. Additionally, the current study documents some of the unique challenges and issues in treating Mormon patients.

First episode of major depressive disorder and vascular factors in coronary artery disease patients: Baseline characteristics and response to antidepressant treatment in the CREATE trial

Objective The CREATE trial reported that coronary artery disease (CAD) patients suffering from a first depression derived less benefit from citalopram relative to placebo than those with a recurrent depression. The present investigation sought to determine whether the differential benefit of citalopram between those with a first depression and those with recurrent depression could be explained by indicators of vascular depression and cardiac disease severity. Methods Secondary analyses of data from CREATE, a 12-week, randomized placebo-controlled trial of 284 patients with major depressive disorder and CAD were used. Recurrence subgroups were compared on baseline characteristics reflecting vascular depression and cardiac disease severity. Outcome measures were the mean change from baseline to 12 weeks on the 24-item Hamilton Depression Rating Scale administered centrally by telephone. ANCOVA was used to assess the potential interaction of each baseline variable with citalopram/placebo treatment in predicting outcomes. Results Few baseline differences differentiated patients with a first versus recurrent depression, and none accounted for the differential treatment efficacy in these subgroups. Patients with a cardiac event in the past 6 months ( P=.02) and taking angiotensin-converting enzyme inhibitors ( P=.03) experienced less change with citalopram relative to placebo. Older age, worse functional status, taking β-blockers, presence of angina (all P<.05), and later age of first depression ( P=.05) predicted smaller changes in depression, independent of treatment assignment. Conclusions There was limited evidence that the lack of improvement with citalopram relative to placebo in CAD patients with a first depression can be attributed to vascular depression.

Autism Spectrum Disorder: Complex, Controversial, and Confounding

Autism Spectrum Disorders (ASD’s) are complex, controversial, and confounding conditions that have been extensively studied by a multi-disciplinary scientific community dedicated to unraveling the enigma of their etiologies. Investigations havemultiplied exponentially, in parallel with increasingASD prevalence rates. Yet, despite intensive research conducted by investigators whose specific areas of expertise involve one or another of the myriad variables presumed to be causally linked to ASD, the results, while enlightening, have provided few answers to core questions. In retrospect, obstacles to reaching clarity about these debilitating disorders of childhood onset have arisen, in part, due to traditional pursuit by the medical and psychological scientific communities of that one single common pathway or single mechanism that might lead to successful therapeutic intervention. A now voluminous literature has greatly enhanced our understanding about features of these incapacitating childhood conditions and has broadened understanding of underlying neural substrates, genetic contributions, and socioenvironmental moderators. A consequence of this recent work is the recognition that the often successful search in medicine for a unitary answer is unlikely to be applicable to this particular set of puzzling conditions. Regrettably, a prolific literature made possible by an expenditure of enormous professional and financial resources has not yet yielded a clearer picture of core aspects such as causal factors, differential developmental trajectories, treatment efficacy, or potential for recovery. Nonetheless, these foundational studies support a new era of investigation in which it is anticipated that there will be major progress regarding this major public health problem. As the papers in this Special Issue elaborate, the absence of definitive answers necessitates that novel theoretical propositions be formulated, and tested by a scientific community that works in unison to integrate complementary but often disparate data into new, meaningful and replicable hypotheses. A re-conceptualization of the origin of these spectrum disorders is needed and seems possible, building on the existent rich database. The papers in this issue will aid the reader seeking clarity about historical antecedents of autism and ASD research, and about a range of highly pertinent areas of ongoing exploration, including etiologic parameters, neural substrates, diverse phenotypic presentations, genetic markers, variable developmental courses, potential treatments and educational and psychosocial interventions, the possibility of recovery, and impaired or preserved behavioral and neurocognitive outcomes. The search is ongoing for both parsimony and synthesis. The authors for this issue were encouraged to challenge readers to reformulate their own insights and to question preconceived notions about ASD. They did not disappoint. The assembled papers are of interest and value to those engaged either in clinical practice or conducting research, since both pursuits require a full appreciation for the history and course of the ASD diagnosis, knowledge about the associated developmental trajectory, recognition of the many avenues of related investigation, and understanding of contemporary issues and advanced methods now employed to disentangle this morass. The six papers in this special issue review contributions of numerous investigators who have studied specific components of ASD’s, and each presents new theoretical and/or clinical insights, often suggesting reinterpretation of Neuropsychol Rev (2008) 18:271–272 DOI 10.1007/s11065-008-9070-1

Transference Interpretations in Dynamic Psychotherapy: Do They Really Yield Sustained Effects?

Transference interpretation has remained a core ingredient in the psychodynamic tradition, despite limited empirical evidence for its effectiveness. In this study, the authors examined long-term effects of transference interpretations. This was a randomized controlled clinical trial, dismantling design, plus follow-up evaluations 1 year and 3 years after treatment termination. One hundred outpatients seeking psychotherapy for depression, anxiety, personality disorders, and interpersonal problems were referred to the study therapists. Patients were randomly assigned to receive weekly sessions of dynamic psychotherapy for 1 year with or without transference interpretations. Five full sessions from each therapy were rated in order to document treatment fidelity. Outcome variables were the Psychodynamic Functioning Scales (clinician rated) and the Inventory of Interpersonal Problems (self-report). Rating on the Quality of Object Relations Scale (lifelong pattern) and presence of a personality disorder were postulated moderators of treatment effects. Change over time was assessed using linear mixed models. Despite an absence of differential treatment efficacy, both treatments demonstrated significant improvement during treatment and also after treatment termination. However, patients with a lifelong pattern of poor object relations profited more from 1 year of therapy with transference interpretations than from therapy without transference interpretations. This effect was sustained throughout the 4-year study period. The goal of transference interpretation is sustained improvement of the patient's relationships outside of therapy. Transference interpretation seems to be especially important for patients with long-standing, more severe interpersonal problems.

The Efficacy and Tolerability of Methylphenidate and Behavior Modification in Children with Attention-Deficit/Hyperactivity Disorder and Severe Mood Dysregulation

This study examines the tolerability and efficacy of methylphenidate (MPH) and behavior modification therapy (BMOD) in children with attention-deficity/hyperactivity disorder (ADHD) and severe mood dysregulation (SMD). Children (ages 5-12) from a summer program for ADHD were screened for SMD and additional manic-like symptoms using structured assessments and direct clinical interview with the Young Mania Rating Scale (YMRS). The SMD group was comprised of 33 subjects with SMD and elevated YMRS scores (mean = 23.7). They underwent weekly mood assessments plus the daily ADHD measures that are part of the program. The comparison group (n = 68) was comprised of the rest of the program participants. Using a crossover design, all subjects in both groups were treated with three varying intensities of BMOD (no, low, high) each lasting 3 weeks, with MPH dose (placebo, 0.15 mg/kg t.i.d., 0.3mg/kg t.i.d., and 0.6 mg/kg t.i.d.) varying daily within each behavioral treatment. Groups had comparable ADHD symptoms at baseline, with the SMD group manifesting more oppositional defiant disorder/conduct disorder (ODD/CD) symptoms (p < 0.001). Both groups showed robust improvement in externalizing symptoms (p < 0.001). There was no evidence of differential treatment efficacy or tolerability. Treatment produced a 34% reduction in YMRS ratings in SMD subjects (p - 0.001). However, they still exhibited elevated YMRS ratings, more ODD/CD symptoms (p < 0.001), and were more likely to remain significantly impaired at home than non-SMD subjects (p < 0.05). MPH and BMOD are tolerable and effective treatments for children with ADHD and SMD, but additional treatments may be needed to optimize their functioning.

Ethnic Stratification of the Association of RGS4 Variants with Antipsychotic Treatment Response in Schizophrenia

Genetic association studies, including a large meta-analysis, report association of regulator of G protein signaling 4 (RGS4) with schizophrenia in the context of heterogeneity. The central role of RGS4 in regulating signaling via Gi/o coupled neurotransmitter receptors led us to hypothesize that there may be RGS4 genotypes predictive of specific disease phenotypes and antipsychotic treatment responses. Subjects were 678 individuals with schizophrenia who participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Among the 678 subjects, the inferred ancestries were 198 (29%) "Africa only," 397 (59%) "Europe only," and 83 (12%) "Other." Eight single nucleotide polymorphisms (SNPs) spanning RGS4 were genotyped. Multiple linear regression was used to analyze association of RGS4 markers with Positive and Negative Symptoms Scale (PANSS) scores at baseline and throughout antipsychotic treatment. Two consecutive markers within RGS4, rs2661319 and rs2842030, were associated with more severe baseline PANSS total score. Treatment with perphenazine was more effective than treatment with quetiapine (p = .010) or ziprasidone (p = .002) in individuals of inferred African ancestry and homozygous for the rs951439 C allele. RGS4 genotypes predicted both the severity of baseline symptoms and relative responsiveness to antipsychotic treatment. Although these analyses are exploratory and replication is required, these data provide support for RGS4 in schizophrenia pathogenesis and suggest a functional role for RGS4 in differential antipsychotic treatment efficacy of schizophrenia.

C.10.02 Generalised anxiety disorder: differential efficacy of anxiolytic treatments across the range of symptoms and clinical subgroups

C.10.02 Generalised anxiety disorder: differential efficacy of anxiolytic treatments across the range of symptoms and clinical subgroups